Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport.

ABSTRACT

Pregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach for protecting the mother and the neonate from infections remains a high priority. Our work is focused on better understanding the safety and efficacy determinants of IgG antibody preparations when used during pregnancy to benefit the mother and her baby. Using pregnant guinea pigs, we demonstrated that biodistribution of administered IgG to the fetus increases with gestation and results in lower maternal and higher fetal antibody concentrations as pregnancy progresses. Data suggests that partition of antibody immunotherapy to the fetal compartment may contribute to a lower maternal exposure (as measured by the AUC) and a shorter mean residence time of the IgG therapeutic at the end of pregnancy compared to nonpregnant age-matched controls, irrespective of the administered dose. Our studies provide insights on the importance of selecting an efficacious dose in pregnancy that takes into account IgG biodistribution to the fetus. The use of appropriate animal models of placental transfer and infectious disease during pregnancy would facilitate pharmacokinetic modeling to derive a starting dose in clinical trials.